Pioneer Axon - Chemotactic Influences

Chemotactic Influences

A variety of chemotactic cues provide essential signaling directing the directional growth of pioneer axons. Chemotactic cues are unique in that they can be multifunctional and versatile. A single chemotactic cue can both act as an attractant or repellent to pioneer axons, and may work from either a distance or within the immediate vicinity. More specifically, the interactions between chemotactic cues and growth cones can offer a possible explanation for the diversity that is observed in their behavior. Guidance molecules are heavily involved in steering the directions of growth cones. For example, guidance molecules can initiate, extend, stabilize, or retract individual filopodia, as well as attract various adhesion molecules to impact their physical state.

Some of the various chemotactic cues that have been explored in the mechanisms of pioneer axons include netrin, ephrin, semaphorin, Slit-Robo, and Notch. Receptors for these molecules have also been studied. Netrins primarily function as attractions of pioneer axons towards the midline. They can act from a distance as much as a few millimeters, as well as act in short range. Netrins can also act as a repellant. Unique among chemoattractants is that the function of netrin has been conserved among a variety of species across 600 million years. Like netrin, ephrin can function as both an attractant and repellant. Ephrins primarily play a role in setting a gradient along the anterior-poster axis for the guidance of developing retinal axons. Semaphorins, which were first identified on specific axons in the grasshopper CNS, function primarily as short-range inhibitory cues that steer pioneer axons away from less ideal regions. Receptor complexes for semaphorins include neuropilins and plexins

The Slit-Robo cell signaling pathway plays an important role in guiding pioneer axons, especially pioneer longitudinal axons. These axons, which function to connect major parts of the CNS, are mainly present during embryonic development. The Slit family mainly functions as a repellent towards longitudinal axons, guiding them away from the ventral midline. The loss of Slit in Drosophila caused the presence of longitudinal axons in the midline. In conjunction with the Robo receptor, Slit signaling played a role in determining tract positions parallel to the midline for longitudinal axons to follow during development. The loss of either Slit or Robo caused dysfunction in the development of longitudinal pioneer neurons in the midbrain and hindbrain of Drosophila. Furthermore, it has been shown that Robo plays a diversified role in pioneer axon guidance in different areas of the brain during embryonic development. Primarily, Robo 1 is crucial towards pioneer longitudinal axon guidance in the ventral tract, while Robo 2 is important in the dorsal tract.

The signaling associated with the receptor Notch, as well as non-canonical Notch/Abl signaling, have been shown to play a role in the development of longitudinal pioneer neurons in the Drosophila ventral nerve cord. The Notch receptor has been shown to interact with interface glia to form a path that longitudinal pioneer neurons can follow. Notch/Abl signaling in the pioneer neurons increases the motility of the growth cones of longitudinal pioneer axons while stimulating filopodia development. It has also been noted that Notch signaling is also important in the migration of neurons in the mammalian cortex.